We have developed a new method of imaging the mechanical properties of tissues based on very brief (< 1ms) and localized applications of acoustic radiation force and the ultrasonic measurement of the associated tissues' responses to that force. Initial results with this technique demonstrate its ability to image mechanical properties of the medial and adventitial layers within ex vivo and in vivo arteries, and to distinguish hard and soft atherosclerotic plaques from normal vessel wall. We have labeled this method Acoustic Radiation Force Impulse (ARFI) imaging, and are poised to develop a real-time ARFI imaging system utilizing a modified commercial ultrasonic scanner and transducers. We propose studies to develop and evaluate this new technique in the characterization of diffuse and focal atherosclerosis. We propose phantom trials and finite element simulations to guide signal acquisition and processing methods, to explore the fundamental issues of resolution and contrast, and to derive mechanical properties from tissue responses to ARFI excitations containing both inertial and viscoelastic components. We propose ex vivo and in vivo trials in the popliteal and femoral arteries to assess the relationship between the mechanical properties of healthy and diseased arteries provided by this new method and those obtained by alternative methods. We propose clinical trials to assess the relationship between ARFI-derived measures of vascular disease and other methods based on ultrasonic imaging and physical examinations.